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1r6u

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Revision as of 13:20, 16 December 2020

Crystal structure of an active fragment of human tryptophanyl-tRNA synthetase with cytokine activity

Structural highlights

1r6u is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	1r6t, 1n3l, 1ntg
Gene:	WARS (HUMAN)
Activity:	Tryptophan--tRNA ligase, with EC number 6.1.1.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SYWC_HUMAN] Isoform 1, isoform 2 and T1-TrpRS have aminoacylation activity while T2-TrpRS lacks it. Isoform 2, T1-TrpRS and T2-TrpRS possess angiostatic activity whereas isoform 1 lacks it. T2-TrpRS inhibits fluid shear stress-activated responses of endothelial cells. Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression.^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Higher eukaryote tRNA synthetases have expanded functions that come from enlarged, more differentiated structures that were adapted to fit aminoacylation function. How those adaptations affect catalytic mechanisms is not known. Presented here is the structure of a catalytically active natural splice variant of human tryptophanyl-tRNA synthetase (TrpRS) that is a potent angiostatic factor. This and related structures suggest that a eukaryote-specific N-terminal extension of the core enzyme changed substrate recognition by forming an active site cap. At the junction of the extension and core catalytic unit, an arginine is recruited to replace a missing landmark lysine almost 200 residues away. Mutagenesis, rapid kinetic, and substrate binding studies support the functional significance of the cap and arginine recruitment. Thus, the enzyme function of human TrpRS has switched more to the N terminus of the sequence. This switch has the effect of creating selective pressure to retain the N-terminal extension for functional expansion.

Functional and crystal structure analysis of active site adaptations of a potent anti-angiogenic human tRNA synthetase.,Yang XL, Guo M, Kapoor M, Ewalt KL, Otero FJ, Skene RJ, McRee DE, Schimmel P Structure. 2007 Jul;15(7):793-805. PMID:17637340^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wakasugi K, Slike BM, Hood J, Otani A, Ewalt KL, Friedlander M, Cheresh DA, Schimmel P. A human aminoacyl-tRNA synthetase as a regulator of angiogenesis. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):173-7. Epub 2002 Jan 2. PMID:11773626 doi:10.1073/pnas.012602099
↑ Bange FC, Flohr T, Buwitt U, Bottger EC. An interferon-induced protein with release factor activity is a tryptophanyl-tRNA synthetase. FEBS Lett. 1992 Mar 30;300(2):162-6. PMID:1373391
↑ Otani A, Slike BM, Dorrell MI, Hood J, Kinder K, Ewalt KL, Cheresh D, Schimmel P, Friedlander M. A fragment of human TrpRS as a potent antagonist of ocular angiogenesis. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):178-83. Epub 2002 Jan 2. PMID:11773625 doi:10.1073/pnas.012601899
↑ Tzima E, Reader JS, Irani-Tehrani M, Ewalt KL, Schwartz MA, Schimmel P. Biologically active fragment of a human tRNA synthetase inhibits fluid shear stress-activated responses of endothelial cells. Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14903-7. Epub 2003 Nov 20. PMID:14630953 doi:10.1073/pnas.2436330100
↑ Yang XL, Guo M, Kapoor M, Ewalt KL, Otero FJ, Skene RJ, McRee DE, Schimmel P. Functional and crystal structure analysis of active site adaptations of a potent anti-angiogenic human tRNA synthetase. Structure. 2007 Jul;15(7):793-805. PMID:17637340 doi:10.1016/j.str.2007.05.009

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1r6u"

@@ Line 1: / Line 1: @@
 ==Crystal structure of an active fragment of human tryptophanyl-tRNA synthetase with cytokine activity==
-<StructureSection load='1r6u' size='340' side='right' caption='[[1r6u]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='1r6u' size='340' side='right'caption='[[1r6u]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1r6u]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R6U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1R6U FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1r6u]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R6U OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1R6U FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TYM:TRYPTOPHANYL-5AMP'>TYM</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TYM:TRYPTOPHANYL-5AMP'>TYM</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1r6t|1r6t]], [[1n3l|1n3l]], [[1ntg|1ntg]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1r6t|1r6t]], [[1n3l|1n3l]], [[1ntg|1ntg]]</div></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">WARS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tryptophan--tRNA_ligase Tryptophan--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.2 6.1.1.2] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1r6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r6u OCA], [http://pdbe.org/1r6u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1r6u RCSB], [http://www.ebi.ac.uk/pdbsum/1r6u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1r6u ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1r6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r6u OCA], [http://pdbe.org/1r6u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1r6u RCSB], [http://www.ebi.ac.uk/pdbsum/1r6u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1r6u ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 34: / Line 34: @@
 ==See Also==
-*[[Aminoacyl tRNA Synthetase|Aminoacyl tRNA Synthetase]]
+*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
 == References ==
 <references/>
@@ Line 40: / Line 40: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Tryptophan--tRNA ligase]]
 [[Category: McRee, D E]]

1r6u

From Proteopedia

Revision as of 13:20, 16 December 2020

Crystal structure of an active fragment of human tryptophanyl-tRNA synthetase with cytokine activity

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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